One other major approach taken to understand eosinophil activation and regulation is a genetic approach in which we have identified a large kindred with familial hypereosinophilia. This syndrome is autosomal dominant and has allowed physical linkage of the responsible gene to chromosome 5 near to marker D5S1505. There are a number of genes in the area, including that for interleukin 5, but subsequent complete sequencing of the IL-5, IL-3 and GM-CSF gene and their promotes has not identified the candidate gene or mutation. Over the past several years an integrated approach to this disorder has been taken by studying close to 50 members of the kindred. Data collected on their cells and eosinophils have suggested that their eosinophils are without major activation phenotypes (based on cell surface marker expression, electron microscopy, eosinophil survival assays) and microarray analysis has indicated several possible candidate genes. Other hypereosinophilic conditions have been studied extensively, and we have identified new markers that distinguish between a myeloproliferative and a lymphoproliferative form of the Hyperosinophilic Syndrome. Having made this distinction, we have instituted new therapies for the treatment of each of these forms. The interaction between helminth infeciton and allergic disease has been studied using epidemiological tools coupled with physiological measurements of allergic disease and immunological assessments. We have demonstrated that chronic helminth infection protects against allergic diseases.